RARE DISEASE
Lead poisoning
Lead poisoning
Lead poisoning
Synonyms: Lead intoxication, Plumbism, Saturnism
Synonyms: Lead intoxication, Plumbism, Saturnism
Synonyms: Lead intoxication, Plumbism, Saturnism
Drug discovery
3
drugs
With orphan designations
Overview
Lead poisoning is a systemic toxicosis caused by lead accumulation, primarily affecting neurological development in children and cardiovascular/renal function in adults. Exposure occurs through lead-based paint, contaminated soil/water, and occupational sources. Diagnosis relies on venous blood lead levels (BLL), with treatment focused on exposure cessation and chelation therapy for BLL ≥45 μg/dL. Neurocognitive effects are often irreversible, emphasizing prevention [1][6][15][16].
Population
Children <6 years account for 80% of global cases due to hand-to-mouth behavior and higher absorption rates [2][9]
High-risk groups: Residents of pre-1978 housing, battery/recycling workers, and communities with poor lead regulation [7][12][17]
800 million+ children globally have BLL ≥5 μg/dL; 30x higher prevalence in low-income countries [9][14]
Burden
Therapies
Primary intervention: Source identification/removal + nutritional optimization (iron/calcium) [6][8][11]
Chelation 1) Oral DMSA for BLL 45-69 μg/dL 2) IV CaNa₂EDTA for BLL ≥70 μg/dL or encephalopathy [3][13][16]
Monitoring: Weekly BLL checks during chelation + environmental hazard mitigation [6][11]
Categories: rare disorders due to toxic effects
Research Papers
1,466 drug discovery papers about Lead poisoning, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,466 drug discovery papers about Lead poisoning, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2022-05-31 | Oyster (Crassostrea gigas) ferritin can efficiently reduce the damage of Pb2+in vivo by electrostatic attraction.
Heavy metal ions pollution can cause damage to human body through food, so the development of a new kind of macromolecular that can remove heavy metal ions damage has a good application prospect. The possibilities of removing heavy metal ions from food system with ferritin were studied in this paper. In this study, oyster ferritin (GF1) can resistant to denaturation induced by Pb2+, Cd2+, Cr3+ and still maintains its basic structure. GF1 can bind more Pb2+, Cd2+, Cr3+ than recombinant human H-chain ferritin (rHuHF), especially Pb2+, and the findings suggest that each GF1 can capture about 51.42 Pb2+ in solution. The hard and soft acids and base also verifies that Pb2+ have stronger binding ability to the key amino acids at the outer end of the three-fold symmetry channel. Cells preprotected by ferritin could resistant to heavy metal ions. And GF1 can reduce the high blood lead in mice and may play a role in alleviating lead poisoning in vivo. All findings demonstrated that GF1 can be used as a novel macromolecule to bind heavy metal ions, and the study can broaden the research scope of ferritin in contaminated food systems.
2021-12-21 | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning.
The heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform and Drosophila melanogaster fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which represented the presence of Pb in the tested samples in different spatial dimensions. Using iPSC-derived cardiomyocytes, the relationship between beating activity (20-24 beats per minute, bpm) determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 was revealed from simultaneous measurements. Pb (50 μM) affected the beating activity of cardiomyocytes, whereas two drugs that stop the entry of Pb differentially affected this beating activity: verapamil (2 μM) did not reverse the cessation of beating, whereas 2-APB (50 μM) partially restored this activity (16 bpm). The results clearly demonstrate the potential of this biosensor system as an anti-Pb drug screening application. In the Drosophila model, Pb was detected within the adult brain or larval central nervous system (Cha-gal4 > UAS-Met-lead 1.44 M1) using fast epifluorescence and high-resolution two-photon 3D FRET ratio image systems. The tissue-specific expression of Pb biosensors provides an excellent opportunity to explore the possible Pb-specific populations within living organisms. We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning and advanced research on Pb neurotoxicology.
2021-07-30 | Harnessing Peptides against lead pollution and poisoning: Achievements and prospects.
Among the broad applicability of peptides in numerous aspects of life and technologies, their interactions with lead (Pb), one of the most harmful substances to the environment and health, are constantly explored. So far, peptides were developed for environmental remediation of Pb-contaminations by various strategies such as hydrogelation and surface display. They were also designed for Pb detection and sensing by electrochemical and fluorescent methods and for modeling natural proteins that involve in mechanisms by which Pb is toxic. This review aims at summarizing selected examples of these applications, manifesting the enormous potential of peptides in the combat against Pb pollution. Nevertheless, the absence of new medicinal treatments against Pb poisoning that are based on peptides is noticeable. An overview of previous achievements utilizing Pb-peptide interactions towards various goals is presented and can be therefore leveraged to construct a useful toolbox for the design of smart peptides as next-generation therapeutics against Pb.
2019-11-04 | Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases.
While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases. Therapeutic advances being tested, and arguably useful for a number of the neurodegenerative diseases, include a reduction of excess cerebral TNF, whether directly, with a specific anti-TNF biological agent such as etanercept via Batson's plexus, or indirectly via surgically implanting stem cells. Inhaled salbutamol also warrants investigating further across the neurodegenerative disease spectrum. It is now timely to integrate this range of new information across the neurodegenerative disease spectrum, rather than keep seeing it through the lens of individual disease states.
2016-05-24 | Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.
Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.
small molecules
2026-08-15 | Groundnut Shell-Derived Activated Carbon for Lead (Ii) Removal from Aqueous Solution: A Low-Cost Approach to Mitigating Lead Poisoning
Lead (Pb) contamination is a matter of great concern due to its toxic, non-biodegradable and accumulative nature. In this study, activated carbon was prepared from groundnut shell waste by carbonization at 450 °C followed by chemical activation using phosphoric acid at 500 °C and evaluated for its Pb(II) removal capacity from an aqueous solution. The removal mechanism and effectiveness of the adsorbent as a low-cost adsorbent were determined using batch adsorption experiments. The effects of adsorbent doses (0.10-1.00 g/100mL) and solution pH (2.0-8.0) on the removal of Pb(II) were investigated. It was observed that the removal of Pb(II) increased with an increase in the adsorbent dose and attained maximum removal at 1.00g/100mL with a value of 96.4%. The removal of Pb(II) by the adsorbent was strongly dependent on the initial solution pH as the removal increased with an increase in solution pH from 2 to 6, after which it decreased moderately at pH 8 due to the hydrolysis of Pb(II). The removal capacity of GSAC in this study was comparable and in some cases higher than those reported in the literature for other agricultural wastes such as rice husk and coconut shell activated carbon. Overall, the results obtained show the potential of using groundnut shell waste as a low-cost and easily available adsorbent for the removal of Pb(II). Thus concluding that the utilization of the agricultural waste mentioned above would provide an alternative to the high-cost adsorbents currently used and help in reducing the lead content in water, hence minimizing its harmful effects on health.
2026-07-20 | Caffeic Acid Mitigates Behavioral and Biochemical Alterations in Lead-induced Neurotoxicity in Rats With Possible Involvement of TFEB.
Lead (Pb) neurotoxicity is characterized by persistent cognitive and motor impairments that arise from converging disturbances in mitochondrial function, oxidative balance, and neuroinflammatory signaling. Increasing evidence suggests that these pathological outcomes are closely linked to disruption of Transcription Factor EB (TFEB), a key regulator of autophagy-lysosomal pathways and mitochondrial quality control. Impaired TFEB function can promote the accumulation of dysfunctional mitochondria and perpetuate oxidative and inflammatory cascades, thereby exacerbating Pb-induced neurodegeneration. The present study evaluated whether caffeic acid (CFA) protects against Pb-induced neurotoxicity and investigated the involvement of TFEB signaling in its neuroprotective effects. Wistar rats were exposed to lead acetate (100 mg/kg, p.o.) for 30 days, followed by treatment with caffeic acid (CFA; 20 and 40 mg/kg). To validate the mechanistic role of TFEB, eltrombopag, a TFEB inhibitor, was co-administered in dedicated groups. Behavioral outcomes were assessed using the Morris Water Maze and rota rod tests, and hippocampal and cerebellar tissues were examined for mitochondrial complex I-III activities, oxidative stress indices (TBARS, GSH), and inflammatory mediators (TNF-α, IL-1β, NF-κB). Pb exposure produced marked spatial memory deficits, motor impairment, suppression of mitochondrial complex activities, oxidative imbalance, and enhanced inflammatory signaling. CFA treatment attenuated these alterations; however, these benefits were lost upon TFEB inhibition. Collectively, these findings demonstrate that CFA attenuates Pb-induced behavioral and biochemical alterations and suggest that its neuroprotective effects are mediated, at least in part, through TFEB-associated pathways.
2026-07-15 | THE EFFECT OF CHRONIC LEAD INTOXICATION ON BONE TISSUE METABOLISM AND OSTEOREPARATION: EXPERIMENTAL RATIONALE FOR COMBINED CORRECTIVE THERAPY
<p>Background. Lead is one of the most osteotropic toxicants: up to 90% of the total body burden is deposited within the bone mineral matrix, where it competitively substitutes for Ca2+ in the hydroxyapatite lattice, suppresses osteoblast differentiation and enhances osteoclastogenesis. A pathogenetically grounded correction scheme for lead-induced bone metabolic disturbances, and its relationship to reparative osteogenesis, remain insufficiently studied. Aim — to experimentally assess biochemical bone metabolism markers and reparative osteogenesis under chronic lead intoxication, and to evaluate the efficacy of combined corrective therapy (vitamin D3 + calcium citrate + succinic acid). Materials and methods. Forty-five rats were allocated to three groups (control, Pb-intoxication, Pb-intoxication + correction). Chronic intoxication was induced by lead acetate administered ad libitum via drinking water for 8 weeks; at week 4 a monocortical femoral defect was created in all animals. Serum biochemical markers and cortical bone lead content (ICP-OES) were assessed. Results. The Pb group showed significantly reduced osteoblastic activity (alkaline phosphatase −39%, osteocalcin −54%), hypocalcemia (−25%) and marked bone lead accumulation (244.1±21.0 µg/g). Corrective therapy reduced bone lead deposition by 62% and produced statistically significant partial recovery of the studied biochemical parameters. Conclusion. Chronic lead intoxication produces a complex osteotoxic syndrome with disturbed biochemical markers of reparative osteogenesis; the proposed corrective regimen is pathogenetically justified and may serve as a basis for further clinical development of osteoprotective protocols.</p>
2026-07-12 | Lead Poisoning: Bridging Historical Perspectives, Contemporary Toxicology, and Management Strategies
Lead poisoning represents one of the oldest and most persistent environmental health challenges confronting human civilization, spanning millennia of recognized toxicity yet remaining incompletely resolved in contemporary practice. This comprehensive review examines the multifaceted dimensions of plumbism, from its ancient recognition as a neurotoxic hazard to the modern understanding of its subclinical effects at vanishingly low blood lead concentrations. The etiology of lead exposure encompasses legacy sources such as deteriorating lead-based paint and contaminated plumbing, occupational and avocational hazards, and less ubiquitous but clinically significant exposures from imported goods and traditional remedies. Epidemiological surveillance reveals that hundreds of thousands of children in the United States continue to harbor elevated blood lead concentrations, with disproportionate burden falling upon socioeconomically disadvantaged communities residing in older housing stock. The pathophysiology of lead toxicity is extraordinarily complex, involving interference with sulfhydryl-containing enzymes, disruption of divalent cation homeostasis, and multifaceted organ system dysfunction affecting the neurologic, hematologic, renal, cardiovascular, and endocrine systems. The toxicokinetic profile of lead is characterized by differential absorption, distribution, and elimination in children compared to adults, fundamentally explaining the heightened pediatric vulnerability to this cumulative toxin. Clinical manifestations span a spectrum from asymptomatic elevation to the catastrophic syndrome of acute lead encephalopathy, with the most concerning public health impact being the inverse relationship between blood lead concentration and cognitive function, manifested as measurable decrements in intelligence quotient at levels once considered innocuous. Management strategies emphasize the primacy of source identification and environmental remediation, with chelation therapy reserved for cases of severe toxicity under the guidance of medical toxicologists. The prognosis remains guarded, as many lead-induced neurologic sequelae appear irreversible despite intervention, underscoring the critical importance of primary prevention. Optimizing outcomes requires a coordinated interprofessional approach encompassing healthcare providers, public health officials, environmental specialists, educators, and social services, reflecting the complex interplay of biomedical, environmental, and social determinants that characterize this enduring public health challenge.
2026-07-05 | Ameliorative Effects of Ginkgo biloba on Lead Acetate-Induced Oxidative Stress and Histopathological Damages in Rat Liver, Kidney, and Testis.
Ginkgo biloba is a nutritional supplement known for its antioxidant properties and beneficial effects on different organs. This study aimed to investigate the protective effect of Ginkgo biloba supplementation against acute lead toxicity in rats. Thirty-two male Wistar rats were divided into four groups and treated daily for 7 days. The control group received normal saline (1 mL/day, orally). The model group received lead acetate (50 mg/kg/day, ip) without any treatment, and the model with either ethylenediaminetetraacetic acid (EDTA) (50 mg/kg/day, ip) or Ginkgo biloba (200 mg/kg/day, oral gavage). After 7 days, blood samples were collected, and livers, kidneys, and testes were excised and stored for evaluation of oxidative stress markers and histological assessment. Acute lead acetate administration resulted in significant weight loss, an increase in kidney index, elevated serum creatinine and liver enzyme levels, including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase (AlkP), and extensive histological damage in the liver, kidney, and testicular tissues. Administration of the Ginkgo biloba significantly improved serum creatinine and AlkP, showing greater efficacy than EDTA, and reduced histopathological changes, similar to EDTA, including hepatic vascular congestion and fibrosis, renal dilation of Bowman spaces, and glomerular degeneration. Furthermore, Ginkgo biloba treatment improved Leydig and spermatogonia cell counts. Both Ginkgo biloba and EDTA reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) and catalase activities in these organs. Ginkgo biloba exhibited protective effects against lead-induced hepatic, renal and testicular damage through its ability to reduce oxidative stress damage. These results indicate that Ginkgo biloba may serve as a valuable adjunct therapy for mitigating lead-associated organ damage.
oligonucleotides
2025-10-18 | Dual-Action Cellular Nanoparticles for Effective Lead (Pb2+) Detoxification.
Lead (Pb2+) exposure remains a persistent and serious public health concern due to its widespread presence and profound toxicity. Building on recent advances in toxin-neutralizing cell membrane-coated nanoparticles (CNPs) and the discovery of Pb2+-binding DNA aptamers, we develop dual-action neuron-mimetic CNPs for effective Pb2+ detoxification. In the formulation, the CNPs encapsulate aptamers within metal-organic framework (MOF) cores and coated with membranes derived from SH-SY5Y neuroblastoma cells, two functional components working together to neutralize Pb2+. The resulting constructs, termed Neuron-MOF/aptamer-NPs, exhibit strong Pb2+ binding capacity, excellent colloidal stability in physiological media, and resistance to DNA leakage. In vitro assays identify Neuron-MOF/aptamer-NPs as the most potent formulation, demonstrating dual-action neutralization against Pb2+-induced toxicity, oxidative stress, and lipid peroxidation in SH-SY5Y cells. In vivo, Neuron-MOF/aptamer-NP treatment significantly improves survival in a mouse model of lead poisoning and reduces hematologic, hepatic, and renal damage. Behavioral assessments further confirm the restoration of spatial memory and locomotor function. Neuron-MOF/aptamer-NPs exhibit no signs of acute toxicity in healthy mice. These findings establish Neuron-MOF/aptamer-NPs as a potent and biocompatible therapeutic platform for targeted lead detoxification with systemic and neuroprotective benefits.
2022-05-02 | Targeting CC chemokine ligand (CCL) 20 by miR-143-5p alleviate lead poisoning-induced renal fibrosis by regulating interstitial fibroblasts excessive proliferation and dysfunction.
Environmental lead contamination can cause chronic renal disease with a common clinical manifestation of renal fibrosis and constitutes a major global public health threat. Aberrant proliferation and extracellular matrix (ECM) accumulation in renal interstitial fibroblasts are key pathological causes of renal fibrosis. However, the mechanism underlying lead-induced kidney fibrosis remains unclear. The present study analyzed gene expression prolifes in lead acetate-treated primary mice renal interstitial fibroblasts and confirmed the aberrant expression of CC chemokine ligand (CCL) 20, one of the most obvious up-regulated genes. Analogously, lead acetate exposure dose-dependently increased CCL20 transcription, protein expression and release. Knockdown of CCL20 suppressed lead acetate-induced fibroblast proliferation, hydroxyproline contents, transforming growth factor-beta production and ECM-related protein (Collagen I and fibronectin) expression. Bioinformatics analysis predicted five top miRNAs targeting CCL20. Among them, miR-143-5p expression was dose-dependently decreased in lead acetate-treated fibroblasts. Mechanistically, miR-143-5p directly targeted CCL20. Elevation of miR-143-5p antagonized lead acetate-induced fibroblast proliferation, hydroxyproline and ECM-related protein expression, which were reversed by CCL20 overexpression. Additionally, CCL20 knockdown suppressed lead acetate-mediated Smad2/3 and AKT pathway activation. Notably, miR-143-5p overexpression attenuated the activation of the Smad2/3 and AKT pathway in lead acetate-exposed fibroblasts, which was counteracted by CCL20 elevation. miR-143-5p injection ameliorated renal fibrosis progression in mice in vivo. Thus, targeting CCL20 by miR-143-5p could alleviate renal fibrosis progression by regulating fibroblast proliferation and ECM deposition via the Smad2/3 and AKT signaling, providing a potential therapeutic target for environmental lead contamination-evoked fibrotic kidney disease.
2021-04-28 | Pb exposure triggers MAPK-dependent inflammation by activating oxidative stress and miRNA-155 expression in carp head kidney.
Lead (Pb) is a toxic heavy metal and an aquatic pollutant. Various amounts of heavy metals are released into the environment through industrial discharge, causing excessive contamination of aquatic ecosystems. The head kidney is a unique immune organ of the bony fish and plays an important role in the metabolism of heavy metals. Studies of toxic Pb exposure that have investigated the head kidney of carp are limited. This study was carried out to explore the potential immunotoxicity effects of Pb and the specific related mechanisms in the carp head kidney. Pb poisoning was shown to induce the production of reactive oxygen species (ROS) and increase the expression levels of phosphorylated proteins related to the MAPK pathway, including p38, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK). We also found that microRNA-155 played a key role in regulating the production of inflammatory factors TNF-α, IL-1β, and IL-6, and the pre-miRNA-155 inhibitor reversed the Pb-induced inflammation. In conclusion, these in vitro and in vivo findings suggest that oxidative stress and the MAPKs are involved in the Pb-induced inflammasome response, and the production of microRNA-155 aggravated the occurrence of inflammation in carp head kidney.
2019-03-18 | Chronic lead exposure decreases the expression of Huntingtin-associated protein 1 (HAP1) through Repressor element-1 silencing transcription (REST).
Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability.
2018-12-28 | Lead exposure inhibits expression of SV2C through NRSF.
Lead (Pb) exposure has been shown to affect presynaptic neurotransmitter release in the animal and cell models. The mechanism by which Pb exposure impairs neurotransmitter release remains unknown. In this study, we aimed to investigate the effect of Pb exposure on synaptic vesicle protein 2C (SV2C) and its molecular mechanism. SV2C promoter region contains a neuron-restrictive silencer element (NRSE) binding motif. Neuron-restrictive silencer factor (NRSF) is a transcription repressor that regulates gene expression by binding to NRSE. We also observed whether Pb exposure regulates the transcriptional level of SV2C by influencing the expression of NRSF. Pregnant female rats were exposed to 0, 0.5 and 2.0 g/L lead acetate (PbAc) via drinking water from the first day of gestation until postnatal week 3. Neuro-2a (N2a) cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM PbAc. Our data revealed that the ability of learning and memory in Pb-exposed rats were decreased, Pb exposure decreased SV2C expression and increased NRSF expression in the rat hippocampus and N2a cell. Silencing NRSF can reverse the down-regulation of Pb exposure on SV2C. These results indicate that Pb exposure can inhibit the transcription level of SV2C by up regulating the expression of NRSF. Decreased expression of SV2C can affect neurotransmitter release and synaptic transmission, which affect synaptic plasticity and then result in impairment of learning and memory.
cell therapies
2024-02-09 | Screening and Identification of Probiotic Lactobacilli from the Infant Gut Microbiota to Alleviate Lead Toxicity.
Lead (Pb2+) exposure cause a potential hazard to human health and the ecological environment; however, prevention and treatment of Pb2+ toxicity remain problems. The aim of this study is to isolate a novel probiotic lead (Pb2+)-resistant Lactobacillus strain from the infant gut microbiota and to determine whether they have the probiotic properties and investigate its preventive and therapeutic effects in the early-life Pb2+ exposure mouse model. In the present study, a total of 64 Pb2+-resistant colonies were isolated from the infant gut microbiota. Of these colonies, SYF-08, identified as Lacticaseibacillus casei, exhibited a Pb2+-binding capacity and Pb2+ tolerance. The in vivo study showed that SYF-08 treatment could effectively reduce Pb2+ levels in the blood, alleviate Pb2+ enrichment in bone and brain tissues, and recover the intestinal and brain damage in both dams and offspring. SYF-08 treatment also improved the antioxidant index in the liver and kidney tissues, while increasing the diversity of the intestinal microbiota of the offspring. The results of the in vitro and in vivo studies suggest that SYF-08, isolated from infant fecal samples, is a promising candidate probiotic against Pb2+ toxicity.
2023-02-06 | Lactobacillus fermentum HNU312 alleviated oxidative damage and behavioural abnormalities during brain development in early life induced by chronic lead exposure.
Lead exposure is a global public health safety issue that severely disrupts brain development and causes damage to the nervous system in early life. Probiotics and gut microbes have been highlighted for their critical roles in mitigating lead toxicity. However, the underlying mechanisms by which they work yet to be fully explored. Here, we designed a two-stage experiment using the probiotic Lactobacillus fermentum HNU312 (Lf312) to uncover how probiotics alleviate lead toxicity to the brain during early life. First, we explored the tolerance and adsorption of Lf312 to lead in vitro. Second, the adsorption capacity of the strain was determined and confirmed in vivo. The shotgun metagenome sequencing showed lead exposure-induced imbalance and dysfunction of the gut microbiome. In contrast, Lf312 intake significantly modulated the structure of the microbiome, increased the abundance of beneficial bacteria and short-chain fatty acids (SCFAs)-producing bacteria, and upregulated function-related metabolic pathways such as antioxidants. Notably, Lf312 enhanced the integrity of the blood-brain barrier by increasing the levels of SCFAs in the gut, alleviated inflammation in the brain, and ultimately improved anxiety-like and depression-like behaviours induced by lead exposure in mice. Subsequently, the effective mechanism was confirmed, highlighting that Lf312 worked through integrated strategies, including ionic adsorption and microbiota-gut-brain axis regulation. Collectively, this work elucidated the mechanism by which the gut microbiota mitigates the toxic effects of lead in the brain and provides preventive measures and intervention measures for brain damage due to mass lead poisoning in children.
2022-08-10 | Lactobacillus plantarum WSJ-06 alleviates neurobehavioral injury induced by lead in mice through the gut microbiota.
Chronic lead exposure can result in cognitive dysfunction and behavioral disorders. However, the current treatments for alleviating lead poisoning have many side effects. Previous studies have suggested that probiotics may have the potential to ameliorate neurotoxicity caused by lead exposure. This study determines the alleviating effects of Lactobacillus plantarum WSJ-06 on neurological disorders induced by chronic lead exposure from the perspective of the gut microbiota and serum metabolites. The results showed that treatment with Lactobacillus plantarum WSJ-06 alleviated memory dysfunction and reduced the levels of inflammatory cytokines in the serum and hippocampus induced by lead exposure. In addition, Lactobacillus plantarum WSJ-06 partially restored the lead-induced gut microbiota dysbiosis. It also increased the proportion of some beneficial metabolites in the serum, such as arachidonic acid, tryptophan hydroxylase, serotonin, vitamin B12, trehalose, and kynurenic acid, and decreased some metabolites in the serum, such as LPS 20:5 and L-kynurenine. A correlation analysis further indicated that lead-induced neurobehavioral disorders were related to intestinal microbiota (the [Eubacterium]_siraeum_group, Roseburia, Lactobacillus, etc) and serum metabolites (LPS 20:5, serotonin, vitamin B12, etc). In conclusion, Lactobacillus plantarum WSJ-06 alleviated neuroinflammation and memory impairment caused by lead exposure by modulating the gut microbiota and metabolites in the serum.
2019-10-29 | Bio‐Orthogonal Bacterial Reactor for Remission of Heavy Metal Poisoning and ROS Elimination
Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria-based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide nanoparticles (Ceria) on the surface through a bio-orthogonal reaction, and the complex bioreactor could spontaneously aggregate in organs with high concentration of Pb. Furthermore, the excess Pb is bioadsorbed by bacteria and the concomitant ROS is eliminated by Ceria nanoparticles. In vitro and in vivo studies demonstrate that this integral biotic/abiotic hybrid bioreactor successfully realizes detoxication of Pb and reparation of injury, also accompanied with inappreciable side effects.
2018-04-04 | Surface display of PbrR on Escherichia coli and evaluation of the bioavailability of lead associated with engineered cells in mice
Abstract Human exposure to lead mainly occurs by ingestion of contaminated food, water and soil. Blocking lead uptake in the gastrointestinal tract is a novel prevention strategy. Whole-cell biosorbent for lead was constructed with PbrR genetically engineered on the cell surface of Escherichia coli ( E . coli ), a predominant strain among intestinal microflora, using lipoprotein (Lpp)-OmpA as the anchoring protein. In vitro , the PbrR displayed cells had an enhanced ability for immobilizing toxic lead(II) ions from the external media at both acidic and neutral pH, and exhibited a higher specific adsorption for lead compared to other physiological two valence metal ions. In vivo , the persistence of recombinant E . coli in the murine intestinal tract and the integrity of surface displayed PbrR were confirmed. In addition, oral administration of surface-engineered E . coli was safe in mice, in which the concentrations of physiological metal ions in blood were not affected. More importantly, lead associated with PbrR-displayed E . coli was demonstrated to be less bioavailable in the experimental mouse model with exposure to oral lead. This is reflected by significantly lower blood and femur lead concentrations in PbrR-displayed E . coli groups compared to the control. These results open up the possibility for the removal of toxic metal ions in vivo using engineered microorganisms as adsorbents.
proteins
2022-05-31 | Oyster (Crassostrea gigas) ferritin can efficiently reduce the damage of Pb2+in vivo by electrostatic attraction.
Heavy metal ions pollution can cause damage to human body through food, so the development of a new kind of macromolecular that can remove heavy metal ions damage has a good application prospect. The possibilities of removing heavy metal ions from food system with ferritin were studied in this paper. In this study, oyster ferritin (GF1) can resistant to denaturation induced by Pb2+, Cd2+, Cr3+ and still maintains its basic structure. GF1 can bind more Pb2+, Cd2+, Cr3+ than recombinant human H-chain ferritin (rHuHF), especially Pb2+, and the findings suggest that each GF1 can capture about 51.42 Pb2+ in solution. The hard and soft acids and base also verifies that Pb2+ have stronger binding ability to the key amino acids at the outer end of the three-fold symmetry channel. Cells preprotected by ferritin could resistant to heavy metal ions. And GF1 can reduce the high blood lead in mice and may play a role in alleviating lead poisoning in vivo. All findings demonstrated that GF1 can be used as a novel macromolecule to bind heavy metal ions, and the study can broaden the research scope of ferritin in contaminated food systems.
2021-12-21 | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning.
The heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform and Drosophila melanogaster fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which represented the presence of Pb in the tested samples in different spatial dimensions. Using iPSC-derived cardiomyocytes, the relationship between beating activity (20-24 beats per minute, bpm) determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 was revealed from simultaneous measurements. Pb (50 μM) affected the beating activity of cardiomyocytes, whereas two drugs that stop the entry of Pb differentially affected this beating activity: verapamil (2 μM) did not reverse the cessation of beating, whereas 2-APB (50 μM) partially restored this activity (16 bpm). The results clearly demonstrate the potential of this biosensor system as an anti-Pb drug screening application. In the Drosophila model, Pb was detected within the adult brain or larval central nervous system (Cha-gal4 > UAS-Met-lead 1.44 M1) using fast epifluorescence and high-resolution two-photon 3D FRET ratio image systems. The tissue-specific expression of Pb biosensors provides an excellent opportunity to explore the possible Pb-specific populations within living organisms. We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning and advanced research on Pb neurotoxicology.
2021-07-30 | Harnessing Peptides against lead pollution and poisoning: Achievements and prospects.
Among the broad applicability of peptides in numerous aspects of life and technologies, their interactions with lead (Pb), one of the most harmful substances to the environment and health, are constantly explored. So far, peptides were developed for environmental remediation of Pb-contaminations by various strategies such as hydrogelation and surface display. They were also designed for Pb detection and sensing by electrochemical and fluorescent methods and for modeling natural proteins that involve in mechanisms by which Pb is toxic. This review aims at summarizing selected examples of these applications, manifesting the enormous potential of peptides in the combat against Pb pollution. Nevertheless, the absence of new medicinal treatments against Pb poisoning that are based on peptides is noticeable. An overview of previous achievements utilizing Pb-peptide interactions towards various goals is presented and can be therefore leveraged to construct a useful toolbox for the design of smart peptides as next-generation therapeutics against Pb.
2019-11-04 | Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases.
While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases. Therapeutic advances being tested, and arguably useful for a number of the neurodegenerative diseases, include a reduction of excess cerebral TNF, whether directly, with a specific anti-TNF biological agent such as etanercept via Batson's plexus, or indirectly via surgically implanting stem cells. Inhaled salbutamol also warrants investigating further across the neurodegenerative disease spectrum. It is now timely to integrate this range of new information across the neurodegenerative disease spectrum, rather than keep seeing it through the lens of individual disease states.
2016-05-24 | Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.
Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.
small molecules
2026-08-15 | Groundnut Shell-Derived Activated Carbon for Lead (Ii) Removal from Aqueous Solution: A Low-Cost Approach to Mitigating Lead Poisoning
Lead (Pb) contamination is a matter of great concern due to its toxic, non-biodegradable and accumulative nature. In this study, activated carbon was prepared from groundnut shell waste by carbonization at 450 °C followed by chemical activation using phosphoric acid at 500 °C and evaluated for its Pb(II) removal capacity from an aqueous solution. The removal mechanism and effectiveness of the adsorbent as a low-cost adsorbent were determined using batch adsorption experiments. The effects of adsorbent doses (0.10-1.00 g/100mL) and solution pH (2.0-8.0) on the removal of Pb(II) were investigated. It was observed that the removal of Pb(II) increased with an increase in the adsorbent dose and attained maximum removal at 1.00g/100mL with a value of 96.4%. The removal of Pb(II) by the adsorbent was strongly dependent on the initial solution pH as the removal increased with an increase in solution pH from 2 to 6, after which it decreased moderately at pH 8 due to the hydrolysis of Pb(II). The removal capacity of GSAC in this study was comparable and in some cases higher than those reported in the literature for other agricultural wastes such as rice husk and coconut shell activated carbon. Overall, the results obtained show the potential of using groundnut shell waste as a low-cost and easily available adsorbent for the removal of Pb(II). Thus concluding that the utilization of the agricultural waste mentioned above would provide an alternative to the high-cost adsorbents currently used and help in reducing the lead content in water, hence minimizing its harmful effects on health.
2026-07-20 | Caffeic Acid Mitigates Behavioral and Biochemical Alterations in Lead-induced Neurotoxicity in Rats With Possible Involvement of TFEB.
Lead (Pb) neurotoxicity is characterized by persistent cognitive and motor impairments that arise from converging disturbances in mitochondrial function, oxidative balance, and neuroinflammatory signaling. Increasing evidence suggests that these pathological outcomes are closely linked to disruption of Transcription Factor EB (TFEB), a key regulator of autophagy-lysosomal pathways and mitochondrial quality control. Impaired TFEB function can promote the accumulation of dysfunctional mitochondria and perpetuate oxidative and inflammatory cascades, thereby exacerbating Pb-induced neurodegeneration. The present study evaluated whether caffeic acid (CFA) protects against Pb-induced neurotoxicity and investigated the involvement of TFEB signaling in its neuroprotective effects. Wistar rats were exposed to lead acetate (100 mg/kg, p.o.) for 30 days, followed by treatment with caffeic acid (CFA; 20 and 40 mg/kg). To validate the mechanistic role of TFEB, eltrombopag, a TFEB inhibitor, was co-administered in dedicated groups. Behavioral outcomes were assessed using the Morris Water Maze and rota rod tests, and hippocampal and cerebellar tissues were examined for mitochondrial complex I-III activities, oxidative stress indices (TBARS, GSH), and inflammatory mediators (TNF-α, IL-1β, NF-κB). Pb exposure produced marked spatial memory deficits, motor impairment, suppression of mitochondrial complex activities, oxidative imbalance, and enhanced inflammatory signaling. CFA treatment attenuated these alterations; however, these benefits were lost upon TFEB inhibition. Collectively, these findings demonstrate that CFA attenuates Pb-induced behavioral and biochemical alterations and suggest that its neuroprotective effects are mediated, at least in part, through TFEB-associated pathways.
2026-07-15 | THE EFFECT OF CHRONIC LEAD INTOXICATION ON BONE TISSUE METABOLISM AND OSTEOREPARATION: EXPERIMENTAL RATIONALE FOR COMBINED CORRECTIVE THERAPY
<p>Background. Lead is one of the most osteotropic toxicants: up to 90% of the total body burden is deposited within the bone mineral matrix, where it competitively substitutes for Ca2+ in the hydroxyapatite lattice, suppresses osteoblast differentiation and enhances osteoclastogenesis. A pathogenetically grounded correction scheme for lead-induced bone metabolic disturbances, and its relationship to reparative osteogenesis, remain insufficiently studied. Aim — to experimentally assess biochemical bone metabolism markers and reparative osteogenesis under chronic lead intoxication, and to evaluate the efficacy of combined corrective therapy (vitamin D3 + calcium citrate + succinic acid). Materials and methods. Forty-five rats were allocated to three groups (control, Pb-intoxication, Pb-intoxication + correction). Chronic intoxication was induced by lead acetate administered ad libitum via drinking water for 8 weeks; at week 4 a monocortical femoral defect was created in all animals. Serum biochemical markers and cortical bone lead content (ICP-OES) were assessed. Results. The Pb group showed significantly reduced osteoblastic activity (alkaline phosphatase −39%, osteocalcin −54%), hypocalcemia (−25%) and marked bone lead accumulation (244.1±21.0 µg/g). Corrective therapy reduced bone lead deposition by 62% and produced statistically significant partial recovery of the studied biochemical parameters. Conclusion. Chronic lead intoxication produces a complex osteotoxic syndrome with disturbed biochemical markers of reparative osteogenesis; the proposed corrective regimen is pathogenetically justified and may serve as a basis for further clinical development of osteoprotective protocols.</p>
2026-07-12 | Lead Poisoning: Bridging Historical Perspectives, Contemporary Toxicology, and Management Strategies
Lead poisoning represents one of the oldest and most persistent environmental health challenges confronting human civilization, spanning millennia of recognized toxicity yet remaining incompletely resolved in contemporary practice. This comprehensive review examines the multifaceted dimensions of plumbism, from its ancient recognition as a neurotoxic hazard to the modern understanding of its subclinical effects at vanishingly low blood lead concentrations. The etiology of lead exposure encompasses legacy sources such as deteriorating lead-based paint and contaminated plumbing, occupational and avocational hazards, and less ubiquitous but clinically significant exposures from imported goods and traditional remedies. Epidemiological surveillance reveals that hundreds of thousands of children in the United States continue to harbor elevated blood lead concentrations, with disproportionate burden falling upon socioeconomically disadvantaged communities residing in older housing stock. The pathophysiology of lead toxicity is extraordinarily complex, involving interference with sulfhydryl-containing enzymes, disruption of divalent cation homeostasis, and multifaceted organ system dysfunction affecting the neurologic, hematologic, renal, cardiovascular, and endocrine systems. The toxicokinetic profile of lead is characterized by differential absorption, distribution, and elimination in children compared to adults, fundamentally explaining the heightened pediatric vulnerability to this cumulative toxin. Clinical manifestations span a spectrum from asymptomatic elevation to the catastrophic syndrome of acute lead encephalopathy, with the most concerning public health impact being the inverse relationship between blood lead concentration and cognitive function, manifested as measurable decrements in intelligence quotient at levels once considered innocuous. Management strategies emphasize the primacy of source identification and environmental remediation, with chelation therapy reserved for cases of severe toxicity under the guidance of medical toxicologists. The prognosis remains guarded, as many lead-induced neurologic sequelae appear irreversible despite intervention, underscoring the critical importance of primary prevention. Optimizing outcomes requires a coordinated interprofessional approach encompassing healthcare providers, public health officials, environmental specialists, educators, and social services, reflecting the complex interplay of biomedical, environmental, and social determinants that characterize this enduring public health challenge.
2026-07-05 | Ameliorative Effects of Ginkgo biloba on Lead Acetate-Induced Oxidative Stress and Histopathological Damages in Rat Liver, Kidney, and Testis.
Ginkgo biloba is a nutritional supplement known for its antioxidant properties and beneficial effects on different organs. This study aimed to investigate the protective effect of Ginkgo biloba supplementation against acute lead toxicity in rats. Thirty-two male Wistar rats were divided into four groups and treated daily for 7 days. The control group received normal saline (1 mL/day, orally). The model group received lead acetate (50 mg/kg/day, ip) without any treatment, and the model with either ethylenediaminetetraacetic acid (EDTA) (50 mg/kg/day, ip) or Ginkgo biloba (200 mg/kg/day, oral gavage). After 7 days, blood samples were collected, and livers, kidneys, and testes were excised and stored for evaluation of oxidative stress markers and histological assessment. Acute lead acetate administration resulted in significant weight loss, an increase in kidney index, elevated serum creatinine and liver enzyme levels, including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase (AlkP), and extensive histological damage in the liver, kidney, and testicular tissues. Administration of the Ginkgo biloba significantly improved serum creatinine and AlkP, showing greater efficacy than EDTA, and reduced histopathological changes, similar to EDTA, including hepatic vascular congestion and fibrosis, renal dilation of Bowman spaces, and glomerular degeneration. Furthermore, Ginkgo biloba treatment improved Leydig and spermatogonia cell counts. Both Ginkgo biloba and EDTA reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) and catalase activities in these organs. Ginkgo biloba exhibited protective effects against lead-induced hepatic, renal and testicular damage through its ability to reduce oxidative stress damage. These results indicate that Ginkgo biloba may serve as a valuable adjunct therapy for mitigating lead-associated organ damage.
oligonucleotides
2025-10-18 | Dual-Action Cellular Nanoparticles for Effective Lead (Pb2+) Detoxification.
Lead (Pb2+) exposure remains a persistent and serious public health concern due to its widespread presence and profound toxicity. Building on recent advances in toxin-neutralizing cell membrane-coated nanoparticles (CNPs) and the discovery of Pb2+-binding DNA aptamers, we develop dual-action neuron-mimetic CNPs for effective Pb2+ detoxification. In the formulation, the CNPs encapsulate aptamers within metal-organic framework (MOF) cores and coated with membranes derived from SH-SY5Y neuroblastoma cells, two functional components working together to neutralize Pb2+. The resulting constructs, termed Neuron-MOF/aptamer-NPs, exhibit strong Pb2+ binding capacity, excellent colloidal stability in physiological media, and resistance to DNA leakage. In vitro assays identify Neuron-MOF/aptamer-NPs as the most potent formulation, demonstrating dual-action neutralization against Pb2+-induced toxicity, oxidative stress, and lipid peroxidation in SH-SY5Y cells. In vivo, Neuron-MOF/aptamer-NP treatment significantly improves survival in a mouse model of lead poisoning and reduces hematologic, hepatic, and renal damage. Behavioral assessments further confirm the restoration of spatial memory and locomotor function. Neuron-MOF/aptamer-NPs exhibit no signs of acute toxicity in healthy mice. These findings establish Neuron-MOF/aptamer-NPs as a potent and biocompatible therapeutic platform for targeted lead detoxification with systemic and neuroprotective benefits.
2022-05-02 | Targeting CC chemokine ligand (CCL) 20 by miR-143-5p alleviate lead poisoning-induced renal fibrosis by regulating interstitial fibroblasts excessive proliferation and dysfunction.
Environmental lead contamination can cause chronic renal disease with a common clinical manifestation of renal fibrosis and constitutes a major global public health threat. Aberrant proliferation and extracellular matrix (ECM) accumulation in renal interstitial fibroblasts are key pathological causes of renal fibrosis. However, the mechanism underlying lead-induced kidney fibrosis remains unclear. The present study analyzed gene expression prolifes in lead acetate-treated primary mice renal interstitial fibroblasts and confirmed the aberrant expression of CC chemokine ligand (CCL) 20, one of the most obvious up-regulated genes. Analogously, lead acetate exposure dose-dependently increased CCL20 transcription, protein expression and release. Knockdown of CCL20 suppressed lead acetate-induced fibroblast proliferation, hydroxyproline contents, transforming growth factor-beta production and ECM-related protein (Collagen I and fibronectin) expression. Bioinformatics analysis predicted five top miRNAs targeting CCL20. Among them, miR-143-5p expression was dose-dependently decreased in lead acetate-treated fibroblasts. Mechanistically, miR-143-5p directly targeted CCL20. Elevation of miR-143-5p antagonized lead acetate-induced fibroblast proliferation, hydroxyproline and ECM-related protein expression, which were reversed by CCL20 overexpression. Additionally, CCL20 knockdown suppressed lead acetate-mediated Smad2/3 and AKT pathway activation. Notably, miR-143-5p overexpression attenuated the activation of the Smad2/3 and AKT pathway in lead acetate-exposed fibroblasts, which was counteracted by CCL20 elevation. miR-143-5p injection ameliorated renal fibrosis progression in mice in vivo. Thus, targeting CCL20 by miR-143-5p could alleviate renal fibrosis progression by regulating fibroblast proliferation and ECM deposition via the Smad2/3 and AKT signaling, providing a potential therapeutic target for environmental lead contamination-evoked fibrotic kidney disease.
2021-04-28 | Pb exposure triggers MAPK-dependent inflammation by activating oxidative stress and miRNA-155 expression in carp head kidney.
Lead (Pb) is a toxic heavy metal and an aquatic pollutant. Various amounts of heavy metals are released into the environment through industrial discharge, causing excessive contamination of aquatic ecosystems. The head kidney is a unique immune organ of the bony fish and plays an important role in the metabolism of heavy metals. Studies of toxic Pb exposure that have investigated the head kidney of carp are limited. This study was carried out to explore the potential immunotoxicity effects of Pb and the specific related mechanisms in the carp head kidney. Pb poisoning was shown to induce the production of reactive oxygen species (ROS) and increase the expression levels of phosphorylated proteins related to the MAPK pathway, including p38, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK). We also found that microRNA-155 played a key role in regulating the production of inflammatory factors TNF-α, IL-1β, and IL-6, and the pre-miRNA-155 inhibitor reversed the Pb-induced inflammation. In conclusion, these in vitro and in vivo findings suggest that oxidative stress and the MAPKs are involved in the Pb-induced inflammasome response, and the production of microRNA-155 aggravated the occurrence of inflammation in carp head kidney.
2019-03-18 | Chronic lead exposure decreases the expression of Huntingtin-associated protein 1 (HAP1) through Repressor element-1 silencing transcription (REST).
Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability.
2018-12-28 | Lead exposure inhibits expression of SV2C through NRSF.
Lead (Pb) exposure has been shown to affect presynaptic neurotransmitter release in the animal and cell models. The mechanism by which Pb exposure impairs neurotransmitter release remains unknown. In this study, we aimed to investigate the effect of Pb exposure on synaptic vesicle protein 2C (SV2C) and its molecular mechanism. SV2C promoter region contains a neuron-restrictive silencer element (NRSE) binding motif. Neuron-restrictive silencer factor (NRSF) is a transcription repressor that regulates gene expression by binding to NRSE. We also observed whether Pb exposure regulates the transcriptional level of SV2C by influencing the expression of NRSF. Pregnant female rats were exposed to 0, 0.5 and 2.0 g/L lead acetate (PbAc) via drinking water from the first day of gestation until postnatal week 3. Neuro-2a (N2a) cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM PbAc. Our data revealed that the ability of learning and memory in Pb-exposed rats were decreased, Pb exposure decreased SV2C expression and increased NRSF expression in the rat hippocampus and N2a cell. Silencing NRSF can reverse the down-regulation of Pb exposure on SV2C. These results indicate that Pb exposure can inhibit the transcription level of SV2C by up regulating the expression of NRSF. Decreased expression of SV2C can affect neurotransmitter release and synaptic transmission, which affect synaptic plasticity and then result in impairment of learning and memory.
cell therapies
2024-02-09 | Screening and Identification of Probiotic Lactobacilli from the Infant Gut Microbiota to Alleviate Lead Toxicity.
Lead (Pb2+) exposure cause a potential hazard to human health and the ecological environment; however, prevention and treatment of Pb2+ toxicity remain problems. The aim of this study is to isolate a novel probiotic lead (Pb2+)-resistant Lactobacillus strain from the infant gut microbiota and to determine whether they have the probiotic properties and investigate its preventive and therapeutic effects in the early-life Pb2+ exposure mouse model. In the present study, a total of 64 Pb2+-resistant colonies were isolated from the infant gut microbiota. Of these colonies, SYF-08, identified as Lacticaseibacillus casei, exhibited a Pb2+-binding capacity and Pb2+ tolerance. The in vivo study showed that SYF-08 treatment could effectively reduce Pb2+ levels in the blood, alleviate Pb2+ enrichment in bone and brain tissues, and recover the intestinal and brain damage in both dams and offspring. SYF-08 treatment also improved the antioxidant index in the liver and kidney tissues, while increasing the diversity of the intestinal microbiota of the offspring. The results of the in vitro and in vivo studies suggest that SYF-08, isolated from infant fecal samples, is a promising candidate probiotic against Pb2+ toxicity.
2023-02-06 | Lactobacillus fermentum HNU312 alleviated oxidative damage and behavioural abnormalities during brain development in early life induced by chronic lead exposure.
Lead exposure is a global public health safety issue that severely disrupts brain development and causes damage to the nervous system in early life. Probiotics and gut microbes have been highlighted for their critical roles in mitigating lead toxicity. However, the underlying mechanisms by which they work yet to be fully explored. Here, we designed a two-stage experiment using the probiotic Lactobacillus fermentum HNU312 (Lf312) to uncover how probiotics alleviate lead toxicity to the brain during early life. First, we explored the tolerance and adsorption of Lf312 to lead in vitro. Second, the adsorption capacity of the strain was determined and confirmed in vivo. The shotgun metagenome sequencing showed lead exposure-induced imbalance and dysfunction of the gut microbiome. In contrast, Lf312 intake significantly modulated the structure of the microbiome, increased the abundance of beneficial bacteria and short-chain fatty acids (SCFAs)-producing bacteria, and upregulated function-related metabolic pathways such as antioxidants. Notably, Lf312 enhanced the integrity of the blood-brain barrier by increasing the levels of SCFAs in the gut, alleviated inflammation in the brain, and ultimately improved anxiety-like and depression-like behaviours induced by lead exposure in mice. Subsequently, the effective mechanism was confirmed, highlighting that Lf312 worked through integrated strategies, including ionic adsorption and microbiota-gut-brain axis regulation. Collectively, this work elucidated the mechanism by which the gut microbiota mitigates the toxic effects of lead in the brain and provides preventive measures and intervention measures for brain damage due to mass lead poisoning in children.
2022-08-10 | Lactobacillus plantarum WSJ-06 alleviates neurobehavioral injury induced by lead in mice through the gut microbiota.
Chronic lead exposure can result in cognitive dysfunction and behavioral disorders. However, the current treatments for alleviating lead poisoning have many side effects. Previous studies have suggested that probiotics may have the potential to ameliorate neurotoxicity caused by lead exposure. This study determines the alleviating effects of Lactobacillus plantarum WSJ-06 on neurological disorders induced by chronic lead exposure from the perspective of the gut microbiota and serum metabolites. The results showed that treatment with Lactobacillus plantarum WSJ-06 alleviated memory dysfunction and reduced the levels of inflammatory cytokines in the serum and hippocampus induced by lead exposure. In addition, Lactobacillus plantarum WSJ-06 partially restored the lead-induced gut microbiota dysbiosis. It also increased the proportion of some beneficial metabolites in the serum, such as arachidonic acid, tryptophan hydroxylase, serotonin, vitamin B12, trehalose, and kynurenic acid, and decreased some metabolites in the serum, such as LPS 20:5 and L-kynurenine. A correlation analysis further indicated that lead-induced neurobehavioral disorders were related to intestinal microbiota (the [Eubacterium]_siraeum_group, Roseburia, Lactobacillus, etc) and serum metabolites (LPS 20:5, serotonin, vitamin B12, etc). In conclusion, Lactobacillus plantarum WSJ-06 alleviated neuroinflammation and memory impairment caused by lead exposure by modulating the gut microbiota and metabolites in the serum.
2019-10-29 | Bio‐Orthogonal Bacterial Reactor for Remission of Heavy Metal Poisoning and ROS Elimination
Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria-based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide nanoparticles (Ceria) on the surface through a bio-orthogonal reaction, and the complex bioreactor could spontaneously aggregate in organs with high concentration of Pb. Furthermore, the excess Pb is bioadsorbed by bacteria and the concomitant ROS is eliminated by Ceria nanoparticles. In vitro and in vivo studies demonstrate that this integral biotic/abiotic hybrid bioreactor successfully realizes detoxication of Pb and reparation of injury, also accompanied with inappreciable side effects.
2018-04-04 | Surface display of PbrR on Escherichia coli and evaluation of the bioavailability of lead associated with engineered cells in mice
Abstract Human exposure to lead mainly occurs by ingestion of contaminated food, water and soil. Blocking lead uptake in the gastrointestinal tract is a novel prevention strategy. Whole-cell biosorbent for lead was constructed with PbrR genetically engineered on the cell surface of Escherichia coli ( E . coli ), a predominant strain among intestinal microflora, using lipoprotein (Lpp)-OmpA as the anchoring protein. In vitro , the PbrR displayed cells had an enhanced ability for immobilizing toxic lead(II) ions from the external media at both acidic and neutral pH, and exhibited a higher specific adsorption for lead compared to other physiological two valence metal ions. In vivo , the persistence of recombinant E . coli in the murine intestinal tract and the integrity of surface displayed PbrR were confirmed. In addition, oral administration of surface-engineered E . coli was safe in mice, in which the concentrations of physiological metal ions in blood were not affected. More importantly, lead associated with PbrR-displayed E . coli was demonstrated to be less bioavailable in the experimental mouse model with exposure to oral lead. This is reflected by significantly lower blood and femur lead concentrations in PbrR-displayed E . coli groups compared to the control. These results open up the possibility for the removal of toxic metal ions in vivo using engineered microorganisms as adsorbents.
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Drug Discovery Landscape
3 orphan drug designations for Lead poisoning, including 1 approved therapy.
3 orphan drug designations for Lead poisoning, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Erdosteine | small molecules | EMA | 2012-12-06 | — | Rafifarm SRL |
ALPHA-1-ACID GLYCOPROTEIN | — | EMA | 2003-10-02 | — | Bio Products Laboratory Limited |
Succimer [Chemet capsules] | small molecules | FDA | 1984-05-09 | 1991-01-30 | Bock Pharmacal Company |
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